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Elucidation of the molecular mechanisms by a cyclic peptide, SEK-1005 promotes skin wound healing

Research Project

Project/Area Number 16K15203
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionYamaguchi University

Principal Investigator

INUI Makoto  山口大学, 大学院医学系研究科, 教授 (70223237)

Co-Investigator(Kenkyū-buntansha) 本田 健  山口大学, 大学院医学系研究科, 講師 (30457311)
酒井 大樹  山口大学, 大学院医学系研究科, 助教 (40464367)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords天然環状ペプチド / 創傷治癒促進作用 / 血管誘導作用 / 蛍光標識架橋薬 / 免疫抑制作用 / 皮膚創傷治癒 / ペプチド
Outline of Final Research Achievements

A cyclic peptide, SEK-1005 promotes skin wound healing and angiogenesis. Their mechanisms are, however, unknown. In this study, we found that SEK-1005 promotes migration of skin epithelial cells and vascular epithelial cells. We identified their responsible intracellular signaling. We also found the enhancement of endothelial cell’s tube formation by SEK-1005 and elucidated the responsible intracellular signaling. In order to obtain a tool to identify a SEK-1005-binding protein, we synthesized the modified SEK-1005 to which nitrobenzoxadiazole (NBD) is conjugated. The modified SEK-1005 can transfer a fluorophore, NBD from SEK-1005 to its binding protein.

Academic Significance and Societal Importance of the Research Achievements

本研究は、皮膚創傷治癒促進、血管誘導、免疫抑制など多様な作用を持つ環状ペプチドであるSEK1005に焦点を当て、SEK1005によるTGF-βなどの緩徐な分泌促進というユニークな作用機序を明らかにした。さらに、SEK1005が直接結合する蛋白質を同定するための手段を開発した。これにより、物質的基盤に基づいた作用機序解明のための道を開いた。本研究の成果は、今後、皮膚創傷治癒促進、血管誘導、免疫抑制などが関与する様々な疾患に効く治療薬の開発に結びつく可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 1 results)

  • [Journal Article] PDZRN3 regulates differentiation of myoblasts into myotubes through transcriptional and posttranslational control of Id22019

    • Author(s)
      Takeshi Honda, Makoto Inui
    • Journal Title

      Journal of Cellular Physiology

      Volume: 234 Issue: 3 Pages: 2963-2963

    • DOI

      10.1002/jcp.27113

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct Roles of Small GTPases Rac1 and Rac2 in Histamine H4Receptor?Mediated Chemotaxis of Mast Cells2018

    • Author(s)
      Kuramasu Atsuo、Wakabayashi Mie、Inui Makoto、Yanai Kazuhiko
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics

      Volume: 367 Issue: 1 Pages: 9-19

    • DOI

      10.1124/jpet.118.249706

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated with a Novel Cyclic Peptide without Immunosuppressive Medication2018

    • Author(s)
      Kuwabara Rei、Hamaguchi Masahide、Fukuda Takuya、Sakai Hiroki、Inui Makoto、Sakaguchi Shimon、Iwata Hiroo
    • Journal Title

      Transplantation

      Volume: 102 Issue: 3 Pages: 417-425

    • DOI

      10.1097/tp.0000000000001923

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Co-treatment with a C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation2018

    • Author(s)
      Ishiguro Susumu、Kawabata Atsushi、Zulbaran-Rojas Alejandro、Monson Kelsey、Uppalapati Deepthi、Ohta Naomi、Inui Makoto、Pappas Charalampos G.、Tzakos Andreas G.、Tamura Masaaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 1 Pages: 962-968

    • DOI

      10.1016/j.bbrc.2017.11.102

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A pyridone derivative activates SERCA2a by attenuating the inhibitory effect of phospholamban2017

    • Author(s)
      Kaneko Manami、Yamamoto Hisato、Sakai Hiroki、Kamada Yusuke、Tanaka Toshiki、Fujiwara Shuji、Yamamoto Syunsuke、Takahagi Hiroki、Igawa Hideyuki、Kasai Shizuo、Noda Masakuni、Inui Makoto、Nishimoto Tomoyuki
    • Journal Title

      European Journal of Pharmacology

      Volume: 814 Pages: 1-8

    • DOI

      10.1016/j.ejphar.2017.07.035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 筋芽細胞におけるPDZRN3蛋白質のアポトーシス制御2019

    • Author(s)
      本田 健、品川 右京、水野 優、横須賀 由季、乾 誠
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] トランスグルタミナーゼとヒスタミントランスポーターによるマスト細胞のヒスタミンH4受容体シグナル調節2019

    • Author(s)
      倉増敦朗、乾 誠
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PDZRN3蛋白質による筋芽細胞のアポトーシス制御2018

    • Author(s)
      本田 健、品川 右京、水野 優、横須賀 由季、乾 誠
    • Organizer
      第71回日本薬理学会西南部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PDZRN3 regulates the differentiation of myoblasts into myotubes through Id2-mediated pathway2018

    • Author(s)
      Takeshi Honda, Narumi Nakada, Ryoto Nagai, Yuki Yokosuka, Makoto Inui
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心筋細胞内カルシウム輸送調節の分子機構と心不全治療標的2017

    • Author(s)
      乾 誠
    • Organizer
      第27回病態生理学会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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